Experimental and modeling study of drug release from HPMC-based erodible oral thin films

In this work hydroxypropyl methylcellulose (HPMC) fast-dissolving thin films for oral administration are investigated. Furosemide (Class IV of the Biopharmaceutical Classification System) has been used as a model drug for in vitro release tests using three different set-ups: the Franz cell, the millifluidic flow-through device, and the paddle type dissolution apparatus (USP II). In order to enable drug incorporation within HPMC films, a multifunctional excipient, hydroxypropyl- β -cyclodextrin (HP- β -CD) has been included in the formulation, and the influence of HP- β -CD on film swelling, erosion, and release properties has been investigated. Mathematical models capable of describing the swelling and release processes from HPMC erodible thin films in different apparatuses have been developed. In particular, we propose a new model for the description of drug transport and release in a Franz cell that accounts for the effect of the unavoidable imperfect mixing of the receptor chamber

Freeze-dried nanocomposite gel beads for oral drug delivery. In vitro simulation of gastro-intestinal drug release

We investigated entrapment efficiency, swelling and drug release from freeze-dried gel beads prepared with Gellan gum and a synthetic clay, Laponite. Polymeric beads loaded with two model molecules having different molecular weights were prepared and subjected to in vitro release studies in simulated gastric and intestinal fluids. The experimental observations confirm that laponite may be an effective additive for fabricating sustained drug delivery systems from gellan gum by means of ionotropic gelation and freeze-drying

Cholesterol effect on the specific capacitance of submicrometric DOPC bilayer patches measured by in-liquid scanning dielectric microscopy

The specific capacitance of biological membranes is a key physical parameter in bioelectricity that also provides valuable physicochemical information on composition, phase, or hydration properties. Cholesterol is known to modulate the physicochemical properties of biomembranes, but its effect on the specific capacitance has not been fully established yet. Here we use the high spatial resolution capabilities of in-liquid scanning dielectric microscopy in force detection mode to directly demonstrate that DOPC bilayer patches at 50% cholesterol concentration show a strong reduction of their specific capacitance with respect to pure DOPC bilayer patches. The reduction observed (around 35%) cannot be explained by the small increase in bilayer thickness (around 16%). We suggest that the reduction of the specific capacitance might be due to the dehydration of the polar head groups caused by the insertion of cholesterol molecules in the bilayer. The results reported confirm the potential of in-liquid SDM to study the electrical and physicochemical properties of lipid bilayers at very small scales (down to around 200 nm here), with implications in fields such as biophysics, bioelectricity, biochemistry, and biosensing

The date mussel Lithophaga lithophaga: Biology, ecology and the multiple impacts of its illegal fishery

none8The date mussel Lithophaga lithophaga is an edible endolithic bivalve, protected by the EU Habitats Directive and other international agreements, living inside carbonate rocks. Its illegal harvesting is carried by breaking the rockswhere the bivalve grows. The impact has cascade consequences as it causes permanent changes in the substrate characteristics, the removal of benthic species, a shift from highly complex to structurally simplified habitats. As a result, the rich biodiversity of rocky reefs turns into a biological desert, named “barren”. Alongwith the over exploitation of fish, this practice leads to the increase of sea urchin density and grazing pressure on habitats, hampering the resilience of the associated biodiversity and functions. This paper summarizes the information on date mussel biology, ecology, ecotoxicology, fishery and the legal framework regulating its protection. Evidence indicates that illegal harvesting is still operated and widespread along the Mediterranean and has huge costs in terms of loss of natural capital and ecosystem services, and in terms of active ecological restoration. Two case study areas (the Sorrento and Salento peninsulas) were selected to assess the economic costs of this practice. Tangible economic costs in terms of ecosystems services' loss are huge (from ca. 35,000 to more than 400,000 euros/year in 6.6 km of Sorrento and ca. 1.8 million euros/year along the 69 km of Salento). These costs are, on average, ca. 30 times lower than those of ecosystem restoration. Data mining from websites indicates that date mussels are presently commercialized in hundreds of restaurants in Greece, Balkan countries, Spain and Italy, favoured also by the lack of appropriate consumer information. This practice should be controlled and contrasted at local scale, enforced by national legislations, and implemented by transnational initiatives. Social campaigns are needed to increase public awareness of the serious consequences of date-mussel fishery and consumptionopenAlberto Colletti; Beatrice Savinelli; Giorgia Di Muzio; Lucia Rizzo; Laura Tamburello; Simonetta Fraschetti; Luigi Musco; Roberto DanovaroColletti, Alberto; Savinelli, Beatrice; Di Muzio, Giorgia; Rizzo, Lucia; Tamburello, Laura; Fraschetti, Simonetta; Musco, Luigi; Danovaro, Robert

Dielectric properties and lamellarity of single liposomes measured by in-liquid scanning dielectric microscopy

Liposomes are widely used as drug delivery carriers and as cell model systems. Here, we measure the dielectric properties of individual liposomes adsorbed on a metal electrode by in-liquid scanning dielectric microscopy in force detection mode. From the measurements the lamellarity of the liposomes, the separation between the lamellae and the specifc capacitance of the lipid bilayer can be obtained. As application we considered the case of non-extruded DOPC liposomes with radii in the range ~100-800 nm. Uni-, bi- and tri-lamellar liposomes have been identifed, with the largest population corresponding to bi-lamellar liposomes. The interlamellar separation in the bi-lamellar liposomes is found to be below ~10 nm in most instances. The specifc capacitance of the DOPC lipid bilayer is found to be ~0.75 µF/cm2 in excellent agreement with the value determined on solid supported planar lipid bilayers. The lamellarity of the DOPC liposomes shows the usual correlation with the liposome's size. No correlation is found, instead, with the shape of the adsorbed liposomes. The proposed approach ofers a powerful label-free and non invasive method to determine the lamellarity and dielectric properties of single liposom

Nanoscale mapping of the conductivity and interfacial capacitance of an electrolyte-gated organic field-effect transistor under operation

Versió postprint del document publicat a: https://doi.org/10.1002/adfm.202008032Probing nanoscale electrical properties of organic semiconducting materials at the interface with an electrolyte solution under externally applied voltages is key in the field of organic bioelectronics. It is demonstrated that the conductivity and interfacial capacitance of the active channel of an electrolyte-gated organic field‐effect transistor (EGOFET) under operation can be probed at the nanoscale using scanning dielectric microscopy in force detection mode in liquid environment. Local electrostatic force versus gate voltage transfer characteristics are obtained on the device and correlated with the global current–voltage transfer characteristics of the EGOFET. Nanoscale maps of the conductivity of the semiconducting channel show the dependence of the channel conductivity on the gate voltage and its variation along the channel due to the space charge limited conduction. The maps reveal very small electrical heterogeneities, which correspond to local interfacial capacitance variations due to an ultrathin non-uniform insulating layer resulting from a phase separation in the organic semiconducting blend. Present results offer insights into the transduction mechanism at the organic semiconductor/electrolyte interfaces at scales down to ≈100 nm, which can bring substantial optimization of organic electronic devices for bioelectronic applications such as electrical recording on excitable cells or label-free biosensing

La percezione degli infermieri della morte del paziente oncologico: uno studio qualitativo

Background: Il tema della morte è uno dei fondamentali problemi con cui gli infermieri si possono confrontare nell’agire professionale ed al quale difficilmente si è profondamente e sinceramente preparati. Le difficoltà nel gestire il carico emotivo possono indurlo a sviluppare sentimenti negativi nei confronti della vita e, nella pratica clinica tali da influenzare le capacità di caregiving e la qualità delle cure fornite.  OBIETTIVO: esplorare le percezioni dell’infermiere di fronte alla morte del paziente degente nei reparti di oncologia.  METODO: Studio qualitativo fenomenologico. Il campione di infermieri è stato reclutato presso un I.R.C.C.S. di Roma, un Hospice di Latina ed uno di Rieti. I dati sono stati raccolti mediante mediante focus group. Le interviste semi-strutturate caratterizzate da tre domande costruite ad hoc, audio-registrate, sono state poi trascritte ed analizzate utilizzando il framework analysis approach.  RISULTATI: sono stati condotti in totale 7 focus group con una partecipazione in totale di 39 infemieri. Dall’analisi qualitativa sono emersi quattro temi: “I diversi significati della morte”, “Lo strappo della morte”, “Le variabili percettive della morte”, “Le richieste di aiuto”.  CONCLUSIONI: Lo studio ha evidenziato la necessità di fornire al personale infermieristico un importante supporto psicologico ed emotivo, e di porre attenzione agli elementi organizzativi-ambientali per una migliore gestione dell’evento morte in oncologia.  PAROLE CHIAVE: Infermiere, fine vita, morte,paziente oncologico, studio qualitativo, cure palliative, psiconcologia BACKGROUND: Death is one of the basic theme with which nurses are faced, and for which it is hard for them to prepare deeply and sincerely.  The difficulties in handling the emotional burden can cause them to develop negative feelings towards life and clinical practice, so that it affects their caregiving capacity and the quality of care provided.  AIM: To explore nurses’ perceptions facing the death of a hospitalized oncology patient.  METHODS: Qualitative phenomenological study. The sample of nurses was recruited at IRCCS (Scientific Institute for Research and Healthcare) in Rome, a hospice in Latina and a hospice in Rieti. The data were collected by means of focus groups. The semi-structured interviews featuring three guiding questions constructed for this purpose, were audio-recorded, transcribed, and then analyzed using the analysis framework approach.  RESULTS: In total 7 focus groups were conducted with a total participation of 39 nurses. Four themes emerged from the qualitative analysis: “The different meanings of death”, “The rupture of death”, “The perceptual variables of death”, and “Requests for help”.  CONCLUSION: The study highlighted the need to provide nurses with substantial psychological and emotional support, and give consideration to organizational and environmental factors for better management of the event of death in oncology.  KEY WORDS: Nurse, end of life, nurses perception, death, oncology patient, qualitative study, palliative care, psycho-oncology&nbsp

Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram

IntroductionIdentifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.Patients and methodsWe retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.ResultsA total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36–0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram.ConclusionsPrior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome

Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network

Background and objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability. Methods: A cross-sectional retrospective study with molecular and clinical data collected in an anonymized database was performed. Results: A total of 723 Italian patients with SPAST-HSP (58% men) from 316 families, with a median age at onset of 35 years, were included. Penetrance was 97.8%, with men showing higher Spastic Paraplegia Rating Scale (SPRS) scores (19.67 ± 12.58 vs 16.15 ± 12.61, p = 0.009). In 26.6% of patients with SPAST-HSP, we observed a complicated phenotype, mainly including intellectual disability (8%), polyneuropathy (6.7%), and cognitive decline (6.5%). Late-onset cases seemed to progress more rapidly, and patients with a longer disease course displayed a more severe neurologic disability, with higher SPATAX (3.61 ± 1.46 vs 2.71 ± 1.20, p &lt; 0.001) and SPRS scores (22.63 ± 11.81 vs 12.40 ± 8.83, p &lt; 0.001). Overall, 186 different variants in the SPAST gene were recorded, of which 48 were novel. Patients with SPAST-HSP harboring missense variants displayed intellectual disability (14.5% vs 4.4%, p &lt; 0.001) more frequently, whereas patients with truncating variants presented more commonly cognitive decline (9.7% vs 2.6%, p = 0.001), cerebral atrophy (11.2% vs 3.4%, p = 0.003), lower limb spasticity (61.5% vs 44.5%), urinary symptoms (50.0% vs 31.3%, p &lt; 0.001), and sensorimotor polyneuropathy (11.1% vs 1.1%, p &lt; 0.001). Increasing disease duration (DD) and abnormal motor evoked potentials (MEPs) were also associated with increased likelihood of worse disability (SPATAX score&gt;3). Discussion: The SPAST-HSP phenotypic spectrum in Italian patients confirms a predominantly pure form of HSP with mild-to-moderate disability in 75% of cases, and slight prevalence of men, who appeared more severely affected. Early-onset cases with intellectual disability were more frequent among patients carrying missense SPAST variants, whereas patients with truncating variants showed a more complicated disease. Both longer DD and altered MEPs are associated with worse disability